Gene Spectrum and Clinical Traits of Nine Patients With Oocyte Maturation Arrest.
Gene Spectrum and Clinical Traits of Nine Patients With Oocyte Maturation Arrest.
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9例卵母细胞成熟停滞患者的基因谱和临床特征
DOI：
10.3389/fgene.2022.772143
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发表时间：
2022
影响因子：
3.7
通讯作者：
Niu W
中科院分区：
文献类型：
--
作者：
Huo M;Zhang Y;Shi S;Shi H;Liu Y;Zhang L;Wang Y;Niu W
背景：卵母细胞成熟停滞是一种产生未成熟卵母细胞，体外培养后不能成熟，导致女性原发不孕的疾病。我们旨在总结本中心9例有代表性的患者，回顾分析卵母细胞成熟停滞的遗传变异和临床特征。方法：对9个卵母细胞成熟停滞家系进行调查分析。对先证者进行全外显子测序(WES)以检测致病变异。桑格测序证实了WES在患者和可获得的父母中的发现。用Exac数据库检索变异频率。根据美国医学遗传学和基因组学学会(ACMG)的说法，通过致病性和保守性预测分析对这些变异进行了评估。用光学显微镜观察卵母细胞的表型，并分析表型与基因的相关性。结果：在9例患者中检测到5个基因的9个致病变异，其中3个是新的变异，包括PATL2[c.1374A>；G(p.Ile458Met)]和[1289-1291del TCC(p.Leu430del)]和ZP2[c.1543C>；T(p.Pro515Ser)]。预测有9个变异是致病的，导致不同类型的卵母细胞成熟停滞和临床表型。结论：发现了3个新的致病变异体，使基因变异谱得以扩展。PATL2、TUBB8和ZP1∼3基因的相关致病突变是导致卵母细胞成熟停滞的重要原因。
Background: Oocyte maturation arrest is a disease that produces immature oocytes and cannot be mature after culturing in vitro, which leads to female primary infertility. We aimed to summarize nine representative patients in our center to retrospectively analyze the genetic variants and clinical characteristics of oocyte maturation arrest. Methods: This study examined and analyzed nine families with oocyte maturation arrest. Whole-exome sequencing (WES) of the probands was performed to detect the pathogenic variants. Sanger sequencing verified the WES findings in patients and available parents. ExAC database was used to search the variant frequency. The variants were assessed by pathogenicity and conservational property prediction analysis and according to the American College of Medical Genetics and Genomics (ACMG). Phenotypes of oocytes were evaluated by a light microscopy, and the phenotype-genotype correlation was also evaluated. Results: Nine pathogenic variants in five genes were detected in nine patients, of which three were novel variants, including PATL2 [c.1374A > G (p. Ile458Met)] and [1289-1291del TCC (p. Leu430del)] and ZP2 [c.1543C > T (p. Pro515Ser)]. Nine variants were predicted to be pathogenic, resulting in different types of oocyte maturation arrest and clinical phenotypes. Conclusion: Three novel pathogenic variants were identified, enabling the expansion of the gene variant spectrum. The related pathogenic mutations of the PATL2, TUBB8, and ZP1∼3 genes were highly suggestive of being causative of oocyte maturation arrest.
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影响因子：
64.8
作者：
Monne, Magnus;Han, Ling;Jovine, Luca
通讯作者：
Jovine, Luca
PATL2 的双等位基因突变导致女性不孕，其特征是卵母细胞成熟停滞
影响因子：
9.8
作者：
Chen, Biaobang;Zhang, Zhihua;Wang, Lei
通讯作者：
Wang, Lei
影响因子：
6.7
作者：
Beall S;Brenner C;Segars J
通讯作者：
Segars J
影响因子：
11.1
作者：
Christou-Kent M;Kherraf ZE;Amiri-Yekta A;Le Blévec E;Karaouzène T;Conne B;Escoffier J;Assou S;Guttin A;Lambert E;Martinez G;Boguenet M;Fourati Ben Mustapha S;Cedrin Durnerin I;Halouani L;Marrakchi O;Makni M;Latrous H;Kharouf M;Coutton C;Thierry-Mieg N;Nef S;Bottari SP;Zouari R;Issartel JP;Ray PF;Arnoult C
通讯作者：
Arnoult C
影响因子：
0.8
作者：
Zheng Zhang;Tao Shangguan;Wei He
通讯作者：
Wei He